Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal.
Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal.
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组胺抑制黑色素浓缩激素系统：对睡眠和唤醒的影响。
DOI：
10.1113/jphysiol.2013.268771
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Xu,Xiangmin
中科院分区：
文献类型：
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作者：
Parks,GregoryS;Olivas,NicholasD;Ikrar,Taruna;Sanathara,NaynaM;Wang,Lien;Wang,Zhiwei;Civelli,Olivier;Xu,Xiangmin
黑色素浓集激素（MCH）神经元表达组胺-3受体（H3 R）mRNA，但不表达组胺-1（H1 R）或组胺-2（H2 R）受体mRNA。组胺通过激活突触后H3 R抑制MCH神经元。这种作用是通过G蛋白依赖性内向整流钾（GIRK）通道介导的。组胺可能在清醒时起到沉默MCH神经元的作用。AbstractMelanin‐concentrating hormone（MCH）‐producing neurons已知调节各种生理功能，如进食，代谢，焦虑和抑郁，以及奖励。最近的研究表明，MCH神经元接收来自几个促进觉醒的大脑区域的投射，并且是快速眼动（REM）睡眠调节的组成部分。在这里，我们在大鼠和小鼠中提供了MCH神经元表达组胺-3受体（H3 R），但不表达组胺-1（H1 R）或组胺-2（H2 R）受体的证据。在MCH神经元中特异性表达报告基因ZsGreen的新型转基因小鼠的脑切片中的电生理记录显示，组胺强烈抑制MCH神经元，这种作用对TTX不敏感，并被胞内存在的GDP-β-S阻断。特异性H3 R激动剂α-甲基组胺模拟组胺的抑制作用，特异性中性H3 R拮抗剂VUF 5681阻断这种作用。Tertiapin Q（TPQ）是一种G蛋白依赖性内向整流钾（GIRK）通道抑制剂，可消除MCH神经元的组胺能抑制。这些结果表明，组胺通过激活GIRK通道通过H3 R直接抑制MCH神经元，并表明唤醒活性组胺能神经元对MCH系统的抑制可能是导致清醒期间MCH神经元沉默的原因，因此可能直接参与睡眠和觉醒的调节。
Key pointsMelanin‐concentrating hormone (MCH) neurons express histamine‐3 receptor (H3R) mRNA but not histamine‐1 (H1R) or histamine‐2 (H2R) receptor mRNA.Histamine inhibits MCH neurons by activating postsynaptic H3R. This effect is mediated through G protein‐dependent inwardly rectifying potassium (GIRK) channels.Histamine may function to silence MCH neurons during wakefulness.AbstractMelanin‐concentrating hormone (MCH)‐producing neurons are known to regulate a wide variety of physiological functions such as feeding, metabolism, anxiety and depression, and reward. Recent studies have revealed that MCH neurons receive projections from several wake‐promoting brain regions and are integral to the regulation of rapid eye movement (REM) sleep. Here, we provide evidence in both rats and mice that MCH neurons express histamine‐3 receptors (H3R), but not histamine‐1 (H1R) or histamine‐2 (H2R) receptors. Electrophysiological recordings in brain slices from a novel line of transgenic mice that specifically express the reporter ZsGreen in MCH neurons show that histamine strongly inhibits MCH neurons, an effect which is TTX insensitive, and blocked by the intracellular presence of GDP‐β‐S. A specific H3R agonist, α‐methylhistamine, mimicks the inhibitory effects of histamine, and a specific neutral H3R antagonist, VUF 5681, blocks this effect. Tertiapin Q (TPQ), a G protein‐dependent inwardly rectifying potassium (GIRK) channel inhibitor, abolishes histaminergic inhibition of MCH neurons. These results indicate that histamine directly inhibits MCH neurons through H3R by activating GIRK channels and suggest that that inhibition of the MCH system by wake‐active histaminergic neurons may be responsible for silencing MCH neurons during wakefulness and thus may be directly involved in the regulation of sleep and arousal.